Regulation of immune responses by IL-15

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyushu University
• Principal Investigator: HISAKATA Yamada Kyushu University, 生体防御医学研究所, 准教授 (20363369)
• Project Period (FY): 2008 – 2010
• Keywords: リウマチ病学

Research Abstract

In order to elucidate the pathogenesis of inflammatory diseases such as rheumatoid arthritis (RA), it is important to understand the mechanism of regulating T cell functions that play central role in immune responses. In the present study, we addressed the role of IL-15, one of the proinflammatory cytokines that are upregulated in RA, in T cell functions in vivo by using mouse models. We found IL-15 is especially important in the development, maintenance, and activation of self-specific T cells.

Research Products

• [Journal Article] Preferential Accumulation of Activated Th1 Cells Not Only in Rheumatoid Arthritis But Also in Osteoarthritis Joints. (2011)
  • Author(s): Yamada H, Nakashima Y, Okazaki K,Mawatari T, Fukushi JI, Oyamada A, Fujimura K, Iwamoto Y, Yoshikai Y.
  • Journal Title: J Rheumatol.[Epub ahead of print]
  • Peer Reviewed
• [Journal Article] IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guerin treatment against bladder cancer. (2011)
  • Author(s): Takeuchi A, Dejima T, Yamada H, Shibata K, Nakamura R, Eto M, Nakatani T, Naito S, Yoshikai Y.
  • Journal Title: Eur J Immunol. 41(1) Pages: 246-51
  • Peer Reviewed
• [Journal Article] CD30 Ligand Is a Target for a Novel Biological Therapy against Colitis Associated with Th17 Responses. (2010)
  • Author(s): Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, Iwakura Y, Yoshikai Y.
  • Journal Title: J Immunol. 185(12) Pages: 7671-7680Nov 10.
  • Peer Reviewed
• [Journal Article] Th17 cells and human arthritic diseases. (2010)
  • Author(s): Yamada H.
  • Journal Title: Nihon Rinsho Meneki Gakkai Kaishi. 33(4) Pages: 214-221
• [Journal Article] CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice. (2010)
  • Author(s): Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, Yoshikai Y.
  • Journal Title: J Immunol. 185(4) Pages: 2222-2230
  • Peer Reviewed
• [Journal Article] Current perspectives on the role of IL-17 in autoimmune disease. (2010)
  • Author(s): Yamada H.
  • Journal Title: J.Inflam Res. 3 Pages: 33-34
  • Peer Reviewed
• [Journal Article] Interleukin-15 is critical in the pathogenesis of influenza A virus-induced acute lung injury. (2010)
  • Author(s): Nakamura R, Maeda N, Shibata K, Yamada H, Kase T, Yoshikai Y.
  • Journal Title: J Virol. 84(11) Pages: 5574-5582
  • Peer Reviewed
• [Journal Article] The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury. (2010)
  • Author(s): Saiwai H, Ohkawa Y, Yamada H, Kumamaru H, Harada A, Okano H, Yokomizo T, Iwamoto Y, Okada S.
  • Journal Title: Am J Pathol. 176(5) Pages: 2352-2366
  • Peer Reviewed
• [Journal Article] Direct recognition of mycobacterial cord factor, trehalose dimycolate, by C-type lectin Mincle. (2009)
  • Author(s): Ishikawa E, Ishikawa T, Morita Y, Toyonaga K, Yamada H, Takeuchi O, Akira S, Kinoshita T, Yoshikai Y. Yamasaki S.
  • Journal Title: J Exp Med. 206(13) Pages: 2879-2888
  • Peer Reviewed
• [Journal Article] Tyrosine kinase 2 plays critical roles in the pathogenic CD4 T cell responses for the development of experimental autoimmune encephalomyelitis. (2009)
  • Author(s): Oyamada A, Ikebe H, Itsumi M, Saiwai H, Okada S, Shimoda K, Iwakura Y, Nakayama K, Iwamoto Y, Yoshikai Y, Yamada H.
  • Journal Title: J Immunol. 183(11) Pages: 7539-7546
  • Peer Reviewed
• [Journal Article] Oral administration of xanthan gum enhances antitumor activity through Toll-like receptor 4. (2009)
  • Author(s): Takeuchi A, Kamiryou Y, Yamada H, Eto M, Shibata K, Haruna K, Naito S, Yoshikai Y.
  • Journal Title: Int Immunopharmacol. 9(13-14) Pages: 1562-1567
  • Peer Reviewed
• [Journal Article] Protective role of Fas-FasL signaling in lethal infection with herpes simplex virus type 2 in mice. (2009)
  • Author(s): Ishikawa T, Yamada H, Oyamada A, Goshima F, Nishiyama Y, Yoshikai Y.
  • Journal Title: J Virol. 83(22) Pages: 11777-11783
  • Peer Reviewed
• [Journal Article] Th17 cells in human rheumatoid arthritis. (2009)
  • Author(s): Yamada H.
  • Journal Title: Nihon Rinsho Meneki Gakkai Kaishi. 32(4) Pages: 249-255
• [Journal Article] IL-15 is critical for the maintenance and innate functions of self-specific CD8(+) T cells. (2009)
  • Author(s): Itsumi M, Yoshikai Y, Yamada H.
  • Journal Title: Eur J Immunol. 39(7) Pages: 1784-1793
  • Peer Reviewed
• [Journal Article] Donor CD4 T Cells Are Critical in Allogeneic Stem Cell Transplantation against Murine Solid Tumor. (2009)
  • Author(s): Kamiryo Y, Eto M, Yamada H, Yajima T, Harano M, Takeuchi A, Tatsugami K, Hamaguchi M, Naito S, Yoshikai Y.
  • Journal Title: Cancer Res. 69(12) Pages: 5151-5158
  • Peer Reviewed
• [Journal Article] IL-15 protects antigen-specific CD8+ T cell contraction after Mycobacterium bovis bacillus Calmette-Guerin infection. (2009)
  • Author(s): Tang C, Yamada H, Shibata K, Yoshida SI, Wajjwalku W, Yoshikai Y.
  • Journal Title: J Leukoc Biol. 86(1) Pages: 187-194
  • Peer Reviewed
• [Journal Article] A novel role of CD30L/CD30 signaling by T-T cell interaction in Th1 response against mycobacterial infection. (2008)
  • Author(s): Tang C, Yamada H, Shibata K, Muta H, Wajjwalku W, Podack ER, Yoshikai Y.
  • Journal Title: J Immunol. 181(9) Pages: 6316-6327
  • Peer Reviewed
• [Journal Article] Identification of CD25+ gammadelta T cells as fetal thymus-derived naturally occurring IL-17 producers. (2008)
  • Author(s): Shibata K, Yamada H, Nakamura R, Sun X, Itsumi M, Yoshikai Y.
  • Journal Title: J Immunol. 181(9) Pages: 5940-5947
  • Peer Reviewed
• [Journal Article] The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. (2008)
  • Author(s): Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, Matsumoto M, Matsuo K, Penninger JM, Takayanagi H, Yokota Y, Yamada H, Yoshikai Y, Inoue J, Akiyama T, Takahama Y.
  • Journal Title: Immunity. 29(3) Pages: 438-450
  • Peer Reviewed
• [Journal Article] Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by gammadelta T cells. (2008)
  • Author(s): Nakamura R, Shibata K, Yamada H, Shimoda K, Nakayama K, Yoshikai Y.
  • Journal Title: J Immunol. 181(3) Pages: 2071-2075
  • Peer Reviewed
• [Journal Article] Comparative histopathological analysis between tenosynovitis and joint synovitis in rheumatoid arthritis. (2008)
  • Author(s): Kaibara N, Yamada H, Shuto T, Nakashima Y, Okazaki K, Miyahara H, Esaki Y, Hirata G, Iwamoto Y.
  • Journal Title: Histopathology. 52(7) Pages: 856-864
  • Peer Reviewed
• [Journal Article] Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. (2008)
  • Author(s): Yamada H, Nakashima Y, Okazaki K, Mawatari T, Fukushi JI, Kaibara N, Hori A, Iwamoto Y, Yoshikai Y.
  • Journal Title: Ann Rheum Dis. 67(9) Pages: 1299-1304
  • Peer Reviewed
• [Presentation] The basic helix-loop-helix protein HES1は自然発生IL-17産生γδT細胞分化に必要である (2010)
  • Author(s): 柴田健輔、山田久方、吉開泰信
  • Organizer: 第21回日本生体防御学会学術総会
  • Place of Presentation: 仙台市
  • Year and Date: 20100722-20100724
• [Presentation] Preferential accumulation of Th1 cells in the joints of rheumatoid arthritis and osteoarthritis. (2010)
  • Author(s): H.Yamada, A.Oyamada, Y.Yoshikai
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-24
• [Presentation] Interleukin-15 is critical in the pathogenesis of influenza A virus-induced acute lung injury. (2010)
  • Author(s): R.Nakamura, N.Maeda, O.Noyori, K.Shibata, H.Yamada, Y.Yoshikai
  • Organizer: 14th International Congress of Immunology.
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-24
• [Presentation] マウスコラーゲン誘導性関節炎におけるTyk2の重要性 (2010)
  • Author(s): 小山田亜希子、藤村謙次郎、岩本幸英、吉開泰信、山田久方
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-04-24
• [Presentation] IL-15は自己抗原特異的CD8T細胞の維持や機能を制御する (2009)
  • Author(s): 逸見百江、吉開泰信、山田久方
  • Organizer: 第20回日本生体防御学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 20090725-20090726
• [Presentation] 関節リウマチの関節内CD4T細胞サブセットの解析 (2009)
  • Author(s): 山田久方、中島康晴、岡崎賢、馬渡太郎、福士純一、小山田亜希子、岩本幸英
  • Organizer: 第53回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京都
  • Year and Date: 20090423-20090426
• [Presentation] IL-15は自己抗原特異的CD8陽性T細胞の維持と自然免疫機能に重要である (2009)
  • Author(s): 山田久方、逸見百江、吉開泰信
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-04
• [Presentation] ヒト関節リウマチとTh17細胞 (2009)
  • Author(s): 山田久方
  • Organizer: 第37回日本臨床免疫学会総会
  • Place of Presentation: 東京都
  • Year and Date: 2009-11-13
• [Presentation] 自己抗原特異的メモリー型T細胞の骨髄由来細胞による正の選択 (2008)
  • Author(s): 山田久方、逸見百江、吉開泰信
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-01
• [Remarks] ホームページ等